{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:03:23Z","timestamp":1780679003530,"version":"3.54.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":133,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011372","name":"RCPA Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011372","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autoantibodies against granulocyte\u2013macrophage colony-stimulating factor (GM-CSF) are the cause of autoimmune pulmonary alveolar proteinosis (aPAP). They are also found in the serum\/plasma of previously immunocompetent patients with disseminated Cryptococcus spp. infection (typically spp. gattii) and disseminated Nocardia spp. infection. Detection of this autoantibody is generally performed through an antibody binding assay, followed by a live-cell\u2013based pSTAT5 neutralization to confirm functional significance of detected autoantibodies. The requirement for a live-cell\u2013based assay increases the technical difficulty of diagnosis and means that this testing is generally only offered in specialist research centres. We report a bioluminescent immunoassay (BLIA) platform, which accurately detects inhibition of GM-CSF detection in serum. The BLIA method has previously been described in detail to detect anti-cytokine autoantibodies against IFN\u03b3. The BLIA platform was able to distinguish 24 blinded disease control samples with 100% accuracy when compared with gold standard testing. We sought referrals for patients with aPAP, Cryptococcus spp. Infection, and Nocardia spp. infection to test the performance of this assay. Positive results were seen in 100% of patients with clinically confirmed aPAP and a proportion of patients with disseminated Cryptococcus or Nocardia spp. infection. We conclude that the BLIA is technically simple, rapid, and easily automatable and could be easily employed in a diagnostic laboratory. The performance characteristics of the BLIA result in rapid and accurate screening of patients with these uncommon autoantibody-mediated conditions, allowing for quick diagnosis and referral for specialist management.<\/jats:p>","DOI":"10.1093\/cei\/uxag027","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:47:16Z","timestamp":1778240836000},"source":"Crossref","is-referenced-by-count":0,"title":["A bioluminescent inhibition immunoassay for detecting GM-CSF inhibitory activity in serum"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-704X","authenticated-orcid":false,"given":"Peter","family":"Bradhurst","sequence":"first","affiliation":[{"name":"Department of Immunology, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Institute of Academic Medicine, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Faculty of Health and Medicine, University of Sydney , Camperdown, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Stoyanov","sequence":"additional","affiliation":[{"name":"Department of Immunology, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Institute of Academic Medicine, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Faculty of Health and Medicine, University of Sydney , Camperdown, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey B","family":"Rosen","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), NIH , Bethesda, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Holland","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), NIH , Bethesda, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas V","family":"Guy","sequence":"additional","affiliation":[{"name":"Department of Immunology, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Institute of Academic Medicine, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Faculty of Health and Medicine, University of Sydney , Camperdown, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00e1s","family":"Urriola","sequence":"additional","affiliation":[{"name":"Department of Immunology, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Institute of Academic Medicine, Royal Prince Alfred Hospital , Camperdown, NSW 2050 ,","place":["Australia"]},{"name":"Faculty of Health and Medicine, University of Sydney , Camperdown, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2026060512320714800_uxag027-B1","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190945","article-title":"GM-CSF in inflammation","volume":"217","author":"Hamilton","year":"2020","journal-title":"J Exp Med"},{"key":"2026060512320714800_uxag027-B2","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/ni.3005","article-title":"Induction of the nuclear receptor PPAR-\u03b3 by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages","volume":"15","author":"Schneider","year":"2014","journal-title":"Nat Immunol"},{"key":"2026060512320714800_uxag027-B3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41572-019-0066-3","article-title":"Pulmonary alveolar proteinosis","volume":"5","author":"Trapnell","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2026060512320714800_uxag027-B4","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1164\/rccm.202112-2742SO","article-title":"Autoimmune pulmonary alveolar proteinosis","volume":"205","author":"McCarthy","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"2026060512320714800_uxag027-B5","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1084\/jem.190.6.875","article-title":"Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte\/macrophage colony-stimulating factor","volume":"190","author":"Kitamura","year":"1999","journal-title":"J Exp Med"},{"key":"2026060512320714800_uxag027-B6","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1056\/NEJMc0904077","article-title":"Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis","volume":"361","author":"Sakagami","year":"2009","journal-title":"N Engl J Med"},{"key":"2026060512320714800_uxag027-B7","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.immuni.2016.10.026","article-title":"GM-CSF: from growth factor to central mediator of tissue inflammation","volume":"45","author":"Becher","year":"2016","journal-title":"Immunity"},{"key":"2026060512320714800_uxag027-B8","doi-asserted-by":"crossref","first-page":"735443","DOI":"10.3389\/fphar.2021.735443","article-title":"GM-CSF: orchestrating the pulmonary response to infection","volume":"12","author":"McCormick","year":"2022","journal-title":"Front Pharmacol"},{"key":"2026060512320714800_uxag027-B9","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s00439-020-02180-0","article-title":"Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?","volume":"139","author":"Ku","year":"2020","journal-title":"Hum Genet"},{"key":"2026060512320714800_uxag027-B10","volume-title":"PLoS Pathogens","author":"Ricafrente","year":"2026"},{"key":"2026060512320714800_uxag027-B11","doi-asserted-by":"crossref","first-page":"752856","DOI":"10.3389\/fimmu.2021.752856","article-title":"The role of GM-CSF autoantibodies in infection and autoimmune pulmonary alveolar proteinosis: a concise review","volume":"12","author":"Ataya","year":"2021","journal-title":"Front Immunol"},{"key":"2026060512320714800_uxag027-B12","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/cid\/ciu968","article-title":"Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated\/extrapulmonary nocardiosis","volume":"60","author":"Rosen","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2026060512320714800_uxag027-B13","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1056\/NEJMoa1913590","article-title":"Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis","volume":"383","author":"Trapnell","year":"2020","journal-title":"N Engl J Med"},{"key":"2026060512320714800_uxag027-B14","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/s12931-022-02103-9","article-title":"Neutralizing GM-CSF autoantibodies in pulmonary alveolar proteinosis, cryptococcal meningitis and severe nocardiosis","volume":"23","author":"Salvator","year":"2022","journal-title":"Respir Res"},{"key":"2026060512320714800_uxag027-B15","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s10096-024-04785-z","article-title":"Disseminated nocardiosis and anti-GM-CSF antibodies","volume":"43","author":"Brugnoli","year":"2024","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2026060512320714800_uxag027-B16","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.cmi.2024.01.018","article-title":"Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: a cohort study","volume":"30","author":"Jiang","year":"2024","journal-title":"Clin Microbiol Infect"},{"key":"2026060512320714800_uxag027-B17","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1007\/s10875-022-01341-2","article-title":"Cryptococcus gattii infection as the Major clinical manifestation in patients with autoantibodies against granulocyte\u2013macrophage colony-stimulating factor","volume":"42","author":"Wang","year":"2022","journal-title":"J Clin Immunol"},{"key":"2026060512320714800_uxag027-B18","first-page":"365","volume-title":"Manual of Molecular and Clinical Laboratory Immunology","author":"Lee","year":"2024"},{"key":"2026060512320714800_uxag027-B19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/cei\/uxae055","article-title":"A homogeneous bioluminescent inhibition immunoassay to detect anti-interferon gamma antibodies","volume":"218","author":"Bradhurst","year":"2024","journal-title":"Clin Exp Immunol"},{"key":"2026060512320714800_uxag027-B20","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41587-021-00878-8","article-title":"Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection","volume":"39","author":"Elledge","year":"2021","journal-title":"Nat Biotechnol"},{"key":"2026060512320714800_uxag027-B21","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1039\/D3SD00126A","article-title":"Therapeutic drug monitoring of immunotherapies with novel Affimer\u2013NanoBiT sensor construct","volume":"3","author":"Campbell","year":"2023","journal-title":"Sens Diagn"},{"key":"2026060512320714800_uxag027-B22","author":"Sun"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cei\/advance-article-pdf\/doi\/10.1093\/cei\/uxag027\/68284563\/uxag027.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/220\/1\/uxag027\/68284563\/uxag027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/220\/1\/uxag027\/68284563\/uxag027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T16:32:16Z","timestamp":1780677136000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/doi\/10.1093\/cei\/uxag027\/8678021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/cei\/uxag027","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"uxag027"}}